| 1. |
- Das, A., et al.
(författare)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 2. |
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| 3. |
- Bauer, M., et al.
(författare)
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Association between polarity of first episode and solar insolation in bipolar I disorder
- 2022
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 160
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
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| 4. |
- Farnocchia, Davide, et al.
(författare)
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International Asteroid Warning Network Timing Campaign: 2019 XS
- 2022
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Ingår i: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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| 5. |
- Weeland, CJ, et al.
(författare)
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The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 70-
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Tidskriftsartikel (refereegranskat)abstract
- Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = −0.15 to −0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.
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| 6. |
- Bera, Anup Kumar, et al.
(författare)
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Morphology induced large magnetic anisotropy in obliquely grown nanostructured thin film on nanopatterned substrate
- 2022
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 581
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Tidskriftsartikel (refereegranskat)abstract
- The artificial tailoring of magnetic anisotropy by manipulating surface and interface morphology is attracting widespread interest for its application in spintronic and magnetic memory devices. Here oblique angle deposition on a nanopatterned rippled substrate is presented as a novel route of inducing large in-plane uniaxial magnetic anisotropy (UMA) in magnetic thin films. For this purpose, Cobalt films and rippled SiO2 substrates have been taken as a model system for the present study. Here, nanopatterned substrates are prepared by low energy ion beam erosion (IBE), above which films are deposited obliquely along and normal to the ripple directions. A clear anisotropy in the growth behavior has been observed due to the inhomogeneous in-plane organization of adatoms in the form of columns. The increased shadowing effect in the films deposited obliquely normal to the direction of the ripple patterns causes preferential coalescence of the columns along the substrate ripples, resulting in stronger in-plane UMA in the film. This peculiarity in magnetic behavior is addressed by considering the morphological anisotropy governed by enhanced shadowing effect, the shape anisotropy and the dipolar interactions among the magnetostatically coupled ripple structure.
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| 7. |
- Caretta, Martina Angela, et al.
(författare)
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Water
- 2022
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Ingår i: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Chudasama, Nishith A., et al.
(författare)
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Preparation of seaweed polysaccharide based hydrophobic composite membranes for the separation of oil/water emulsion and protein
- 2022
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 199, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Agarose is a seaweed-based polysaccharide and is widely used for the separation of nucleic acids in molecular biology. Cross-linked agarose beads are also used as solid-phase matrices in size exclusion chromatography for the separation of proteins. To find the application of agarose for the separation of oil/water emulsion and protein, herein hydrophobic derivative of the seaweed biopolymer [M-W (1.27 +/- 0.17) x 10(-5) g/mol; sulphate content (0.29 +/- 0.09) %, gel strength (2242 +/- 21) g/cm(2)] is prepared by reacting the biopolymer with stearic acid and was used to prepare a composite membrane on polyester fabric. The oil and BSA rejection performance of the composite membrane was greater than 98%. The rejection rate increased with the increase in polymer content in the respective membranes for both oil/water and protein separation. The composite membrane showed a stable oil/water emulsion and protein separation performance over a period of six hours. Due to the biodegradable nature of the major components of the membrane, it has the potential for industrial applications.
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| 9. |
- Kuo, Paulina S., et al.
(författare)
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Observation of Backward-Wave Spontaneous Parametric Downconversion in Sub-µm PPKTP
- 2022
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Ingår i: Frontiers in Optics, FiO 2022. - : Optica Publishing Group (formerly OSA).
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Konferensbidrag (refereegranskat)abstract
- We observed backward-wave spontaneous parametric downconversion in subµm periodically poled Rb-doped KTP. Pumped at 800 nm, forward-wave signal at 1400 nm and backward-wave idler at 1868 nm were obtained.
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| 10. |
- Manjunatha, N. K., et al.
(författare)
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A potent anesthetic drug salt: experimental and computational studies
- 2022
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Ingår i: Journal of Molecular Structure. - : Elsevier BV. - 0022-2860 .- 1872-8014. ; 1263
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Tidskriftsartikel (refereegranskat)abstract
- The title compound Ethyl 4-aminobenzoate - 3,5-dinitrosalicylate salt [ES] has been synthesized, crystallized and characterized using FTIR, H-1 NMR, C-13 NMR and confirmed by single crystal X-ray diffraction method. The molecular structure and crystal packing were carried out using theoretical optimization at the DFT level and the concept of atom in molecules (AIM) analysis was performed. Further, the molecular packing is visualized and quantified using Hirshfeld surfaces analysis. The crystal structure is stabilized via intermolecular hydrogen bonds of the type N - H O-center dot center dot center dot and O - H O-center dot center dot center dot. The hydrogen bonding acquires three-dimensional architecture and the molecules in the crystal are connected through C(8) hydrogen motif. The inter contact H center dot center dot center dot O (45.0%) contributes more to the Hirshfeld surfaces and the strength and stability of the multicomponent crystal have been estimated using the energy framework calculation. Further, the biological study of the title compound was studied through antibacterial and antifungal activities. (C) 2022 The Authors. Published by Elsevier B.V.
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